PROJECT SUMMARY The primary goal of this application is to establish a foundation of basic scientists with translational research projects studying developmental mechanisms underlying children's disease by establishing the Center for Pediatric Research. The origin of many pediatric diseases is from altered developmental programming related to the processes of cell proliferation, morphogenesis, migration, differentiation, and programmed death. These developmental processes are at the root of pediatric disease and are disrupted through genetic disorders, aberrant fetal programming, altered growth & development, and environmental pressures. Our multidisciplinary Center applies genetic, biochemical, cell, and molecular approaches across several model organisms to characterize alterations during development as they pertain to pediatric diseases and disorders. For phase II we will continue to build upon the success of phase I efforts to create a critical mass of independently funded investigators within the Center for Pediatric Research by refining our focus to support and mentor junior investigators whose research investigates how key regulators of cellular pliancy contribute to the developmental origin of pediatric disorders. Center success will be achieved through the following Aims: 1) create a supportive environment for the training and mentorship of scientists studying how regulation of cell pliancy contributes to pediatric diseases; 2) utilize and enhance existing resources that will enable pediatric research; 3) expand training and learning opportunities in developmental biology and pediatric disease; and 4) evaluate success of the Center. Through these Aims, the Center for Pediatric Research will develop a strong foundation in basic and translational research by fostering a collaborative environment for scientists and physicians. Strengthened by our institution's strong commitment to children's medicine, we propose that the Center will continue to enhance pediatric research efforts in South Dakota.